The objective of this investigation is the evaluation of the hypothesis that the carbohydrate side chain of glycoproteins of the intercellular matrix may play a central role, through translocation by interactions at the plasma membrane, in growth regulation, tissue organization and/or differentiation, and in vital homeostatic mechanisms such as the regulation of serum protein levels and of the clotting process. We propose to initiate a study of this general hypothesis in two complementary model systems, human fibroblasts in cell culture and mammalian liver. Human fibroblast cultures appear to offer a system which can be developed for the analysis of some, at least, of the elementary steps in "tissue" organization arising from cell-substratum interactions. This would then permit the assessment of the role of the carbohydrate side chain of the glycoproteins of the intercellular matrix in this process. The utilization of this system will require a greatly improved knowledge of the chemistry of the glycoprotein constituents of the matrix secreted by these cells (collagen, basement membrane, plasma membrane, etc.) and of the kinetics of their secretion. At the same time, the wide variety of studies available on special characteristics of the liver plasma membrane, the key metabolic roles of this tissue, its availability in quantity and its capacity for regeneration suggest experimental approaches to the study of glycoprotein-membrane interactions which complement those projected for the fibroblast system. In particular, the studies of Ashwell, Morell and their associates on liver "glycoprotein-receptors" point the way to detailed chemical explorations of macromolecular mechanisms of model glycoprotein-membrane interactions.